Characteristic dysbiosis in patients with type 2 diabetes and hyperuricemia, and the effect of empagliflozin on gut microbiota.

Background: Gut microbiota play a crucial role in metabolic diseases, including type 2 diabetes (T2DM) and hyperuricemia (HUA). One-third of uric acid is excreted into the intestinal tract and further metabolized by gut microbiota. Thus, the gut microbiota might be a new therapeutic target for HUA. Empagliflozin significantly lowers serum uric acid levels and contributes to cardiovascular benefits which are partly attributed to altered gut microbiota. We hypothesize that gut dysbiosis in patients with diabetes and HUA, and the reduction of uric acid by empagliflozin, may be mediated by gut microbiota.

Aim: To investigate dysbiosis in patients with T2DM and HUA, and the effect of empagliflozin on gut microbiota associated with purine metabolism.

Methods: In this age and sex-matched, case-control study, we recruited 30 patients with T2DM and HUA; 30 with T2DM; and 30 healthy controls at the Henan Provincial People's Hospital between February 2019 and August 2023. Nine patients with T2DM and HUA were treated with empagliflozin for three months. Gut microbiota profiles were assessed using the 16S rRNA gene.

Results: Patients with T2DM and HUA had the highest total triglycerides (1.09 mmol/L in heathy control 1.56 mmol/L in T2DM 2.82 mmol/L in T2DM + HUA) and uric acid levels (302.50 μmol/L in heathy control 288.50 μmol/L in T2DM 466.50 μmol/L in T2DM + HUA) among the three groups. The composition of the gut microbiota differed significantly between patients with T2DM and HUA, and those with T2DM/healthy controls ( < 0.05). Notably, patients with T2DM and HUA demonstrated a deficiency of uric acid-degrading bacteria such as , , ( < 0.05). Empagliflozin treatment was associated with significantly reduced serum uric acid levels and purine metabolism-related pathways and genes in patients with T2DM and HUA ( < 0.05).

Conclusion: Gut dysbiosis may contribute to the pathogenesis of HUA in T2DM, and empagliflozin may partly restore the gut microbiota related to uric acid metabolism.